PROJECT SUMMARY/ABSTRACT The goals of this project are to further our understanding of the long-term clinical epidemiology of health outcomes among drug users who are at high risk for HIV. This is important because it will guide clinical practice and health systems planning in the face of the continuing HIV/AIDS epidemic and the evolving epidemic of drug abuse, including opioids. Many HIV-infected persons are living longer than they had in the past, due to the advent and availability of highly active antiretroviral therapy. We have a unique prospective cohort of drug users established in the 1980s, backed by a linked biospecimen repository and permission for indefinite continuing follow-up, established by the NCI and NIDA for the long- term study of drug users. The cohort numbers nearly 11,000 drug users, who are diverse in gender, race, ethnicity and geography, and include large numbers of both HIV-positive and HIV-negative persons. Hepatitis C virus infection is extremely common in these persons. WE SEEK TO UNDERSTAND THE HEALTH OUTCOMES IN THIS COHORT THROUGH TWO AIMS. AIM 1. To determine the epidemiologic features of mortality outcomes associated with HIV among drug users over a 35-year period. This will be accomplished by matching our cohort to vital statistics registry data. AIM 2. To determine the cancer epidemiology, by cancer site, among drug users over a 35-year period, including incidence, stage at diagnosis, treatment regimens, mortality, and HIV-associated risk. This will be accomplished by matching our cohort to cancer registry data. Our project analyses will integrate these two types of data, with stepwise repetition of matching over several years. Mortality data will enable us to more accurately conduct survival analyses on an array of disease outcomes, with a special focus on cancer to identify putative risk factors. This has the potential to assist with the identification of interventions that would reduce disease burden and prolong survival. We will characterize disease outcomes in HIV-positive compared to HIV-negative drug users, accounting for baseline demographic, behavioral, and medical factors. Our cohort uniquely affords the opportunity to study health outcomes over a prolonged time period spanning several decades in both sexes and in underrepresented minority populations. The size of our study and the extent and richness of baseline data will make it a powerful tool in understanding a wide array of disease outcomes. Given the continuing rapid evolution of biotechnology, future research might employ evolving biotechnology to use our biospecimen repository to explore specific disease outcomes we will be identifying. Our cohort has joined the NIDA Genetics Consortium. We will explore joining other consortia which focus on other outcomes, which could amplify the power of those consortia.